ABSTRACT The agrarian political regime of the Khmer Rouge in Cambodia led to the death of nearly 2 million civilians and residual symptoms of distress among many survivors. Recent estimates indicate that nearly 50% of the general population exhibits clinically significant symptoms of trauma-related anxiety and/or depression. Targeting of academic leaders during the genocide further undermined an already vulnerable academic health system needed to support innovations in mental health research and care. Cambodian leadership is committed to resolving the existing mental health gap through strategic partnerships, enhanced capacity building, and adoption of evidence-based treatments (EBT) capable of shifting the trajectory of health and wellness of the population. This application follows on the heels of a successful Phase I program culminating in a clear vision of capacity building needs and national research priorities with high potential for local adoption, scale-up, and sustainability. The proposed application will enrich outcomes from the first phase through completion of three layered and integrated aims. Specific Aim 1 will strengthen the mental health research capacity across performance sites utilizing a combination of standardized content for global mental health and professional development programs tailored for research in Cambodia. Measurable outcomes will support the conceptualization, implementation, and evaluation of externally funded research projects resulting in high impact scientific publications. Specific Aim 2 will examine the acceptability and feasibility of trauma-informed care as a culturally relevant response to trauma exposure. Newly trained and certified research teams led by Cambodian investigators will employ a mixed methods design to evaluate the Missouri Model of trauma-informed care. Specific Aim 3 will determine the effectiveness of a culturally-informed, EBT to reduce symptoms of trauma- related anxiety, depression, and problematic substance use. Preliminary work suggests that the Common Elements Treatment Approach (CETA), a task-sharing EBT has high potential to improve affective disorders and substance use disorders in resource restricted environments. However, studies have only examined CETA administered with ongoing supervision by US-based clinicians. Scale-up and sustainability of CETA in resource restricted environments requires empirical evidence that CETA is effective when administered by providers working in the local health system without ongoing case supervision by international partners. Specific Aim 3 will address this critical issue by comparing CETA modified for independent implementation (mCETA) to standard CETA (sCETA) and waitlist controls. Professional gains obtained from the structured training opportunities will be engaged to complete the clinical trial. Collectively, the structured implementation of this Phase II application will establish a formidable culture of research innovation to address current and future mental health needs of the Cambodian population. Outcomes will inform treatment strategies in other trauma-intense, resource restricted regions of the world.